Damage to mitochondrial DNA has for years been proposed to play a major role in aging process. Recent studies have shown that mutations are in fact involved in some genetic diseases characterized by muscle weakness and encephalopathy. In an effort to develop an animal model to study the causes and consequences of mitochondrial DNA damage, the Wistar rat was examined to assess the presence and/or level of deletions. A 4.8 kb deletion was found and shown to increase markedly with age in rat liver. This deletion corresponds very closely to a 5.0 kb deletion commonly found in humans with mitochondrial myopathies and known to increase with age. Mouse and monkey mitochondrial DNA are also being studied in hopes of developing additional models. This form of mitochondrial DNA damage may be important in muscle weakness and/or atrophy and neuronal degeneration that occurs with age.